Periodic Reporting for period 1 - BioPolyMOF (polyMOFs as promising drug delivery systems for antimicrobial therapy)
Reporting period: 2023-01-01 to 2025-06-30
Metal-organic frameworks (MOFs), built from inorganic units linked by organic polycomplexant ligands, demonstrate exceptional porosity and precisely defined structures that are easily adjustable in composition and topology. These porous crystalline hybrid materials hold promise for a broad spectrum of applications including biomedicine, sensing, and catalysis. However, their translation into clinical and industrial settings has been hindered by concerns regarding stability and toxicity. In response, recent focus has shifted towards MOF-polymer composites, capitalizing on the tunable mechanical and chemical properties of polymers in conjunction with the high porosity and crystallinity of MOFs. Within this context, polyMOFs emerge as promising materials consisting of polymers containing polycomplexant ligands, co-ligands, and metal ions and offering a vast array of novel materials with properties yet to be fully explored. Even though this field is still in its infancy (20 vs over >90000 reported MOFs), it is now booming due to very broad range of new materials with interesting properties to be discovered.
Regarding their applications, all reported polyMOFs are exclusively in the exploratory phase, with 3 reports dealing with their potential application in DDS, proton conductivity and gas separation. In particular, antimicrobial resistance is one of the greatest threats to human health worldwide, becoming imperative to find more efficient novel drugs and/or to improve the current antimicrobial molecules. Drug delivery systems (DDS) appear as a simple and versatile alternative able to solve many of the associated drug drawbacks (e.g. side effects, low solubility, instability, poor bioavailability) while effectively delivering the drugs in the infected area. Thus, PolyMOFs appear as a promising alternative to traditional DDS (lipidic and purely polymeric nanoparticles), which have not fully addressed the challenges of microbial resistance.
In this frame, the objective of BioPolyMOF is to design a robust synthetic strategy for synthesizing novel polyMOFs as drug delivery systems to combat microbial infections. In this regard, the selection of the building blocks is crucial. Therefore, the rational design of these materials entails a metal center with antimicrobial activity, an active co-ligand and a polymer with complexing group.
Regarding their applications, all reported polyMOFs are exclusively in the exploratory phase, with 3 reports dealing with their potential application in DDS, proton conductivity and gas separation. In particular, antimicrobial resistance is one of the greatest threats to human health worldwide, becoming imperative to find more efficient novel drugs and/or to improve the current antimicrobial molecules. Drug delivery systems (DDS) appear as a simple and versatile alternative able to solve many of the associated drug drawbacks (e.g. side effects, low solubility, instability, poor bioavailability) while effectively delivering the drugs in the infected area. Thus, PolyMOFs appear as a promising alternative to traditional DDS (lipidic and purely polymeric nanoparticles), which have not fully addressed the challenges of microbial resistance.
In this frame, the objective of BioPolyMOF is to design a robust synthetic strategy for synthesizing novel polyMOFs as drug delivery systems to combat microbial infections. In this regard, the selection of the building blocks is crucial. Therefore, the rational design of these materials entails a metal center with antimicrobial activity, an active co-ligand and a polymer with complexing group.
For achieving this goal, BioPolyMOF targeted 4 main research and innovation objectives (RIOs):
1. Synthesis and characterization of large library of monomers bearing different polycomplexant ligands (RIO1). During the project, different monomers with coordinating groups were selected bearing complexing groups such as amines, carboxylates, etc.
2. Development of new polymers containing polycomplexant ligands units (RIO2). The development of the polymer platform during the action (> 10 polymers) created a solid foundation for future research. These polymers exhibit promising properties that warrant further investigation, opening new possibilities for advanced applications.
3. Development of a broad library of polyMOFs (RIO3). During this action, 6 novel materials were developed with high stability and promising properties for their application in biomedicine, not only for antimicrobial therapy but as well in other therapies such as cancer therapy.
4. Proof of concept of polyMOFs as DDS, including their in vitro safety and drug loading/release studies (RIO4). All materials developed within the project present high biocompatibility in vitro which confirmed their potential as drug delivery systems. Furthermore, the antimicrobial activity as well as potential in cancer therapy as ROS generators is being tested.
1. Synthesis and characterization of large library of monomers bearing different polycomplexant ligands (RIO1). During the project, different monomers with coordinating groups were selected bearing complexing groups such as amines, carboxylates, etc.
2. Development of new polymers containing polycomplexant ligands units (RIO2). The development of the polymer platform during the action (> 10 polymers) created a solid foundation for future research. These polymers exhibit promising properties that warrant further investigation, opening new possibilities for advanced applications.
3. Development of a broad library of polyMOFs (RIO3). During this action, 6 novel materials were developed with high stability and promising properties for their application in biomedicine, not only for antimicrobial therapy but as well in other therapies such as cancer therapy.
4. Proof of concept of polyMOFs as DDS, including their in vitro safety and drug loading/release studies (RIO4). All materials developed within the project present high biocompatibility in vitro which confirmed their potential as drug delivery systems. Furthermore, the antimicrobial activity as well as potential in cancer therapy as ROS generators is being tested.
BioPolyMOF aimed significant breakthroughs at all relevant scales (Basic and applied research, material transfer and biomaterials). Considering that the polyMOFs field is just blooming, all results obtained here are a great contribution to the scientific community. Also, the knowledge generated in this project could be extended later to other polyMOFs employing different polymers and metals. Within this project, we have developed 6 novel materials (2 MOFs and 4 polyMOFs) that are currently under investigation as drug delivery systems, evaluating their intrinsic antimicrobial activity. Thus, these results could contribute in the fighting of antimicrobial resistance which is identified by the World Health Organization as one of the greatest threats to human health worldwide.
In addition, the project could have a tangible economic impact since the global market for MOF is growing from USD 752 million in 2024 to an estimated USD 2,056 million by 2033 (CAGR of 11.83%). Thus, this project capitalizes on the increasing interest and investment in MOF-based solutions. Also, in the long term, the creation of this new therapeutic platform can also have beneficial impact on other concerning illnesses (e.g. cancer).
Finally, these materials can also be exploited in different strategic fields. Apart from the target DDS, they could present relevant properties for other socioeconomic sectors such as energy (by combining the optoelectronic properties of the cations and the linkers/polymers), sensing (selective adsorption), water remediation (sorption and degradation), and catalytic processes (e.g. H2 production, synthesis of high-value products).
Thus, the research conducted within BioPolyMOF has served as a starting point for unveiling the potential applications of polyMOFs in biomedicine, paving the way for their integration into advanced healthcare solutions.
In addition, the project could have a tangible economic impact since the global market for MOF is growing from USD 752 million in 2024 to an estimated USD 2,056 million by 2033 (CAGR of 11.83%). Thus, this project capitalizes on the increasing interest and investment in MOF-based solutions. Also, in the long term, the creation of this new therapeutic platform can also have beneficial impact on other concerning illnesses (e.g. cancer).
Finally, these materials can also be exploited in different strategic fields. Apart from the target DDS, they could present relevant properties for other socioeconomic sectors such as energy (by combining the optoelectronic properties of the cations and the linkers/polymers), sensing (selective adsorption), water remediation (sorption and degradation), and catalytic processes (e.g. H2 production, synthesis of high-value products).
Thus, the research conducted within BioPolyMOF has served as a starting point for unveiling the potential applications of polyMOFs in biomedicine, paving the way for their integration into advanced healthcare solutions.